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|Authors: ||Pippione, Agnese Chiara|
|Internal Tutor: ||FASANO, MAURO|
|Title: ||Parkinson's disease biomarkers in peripheral blood T lymphocytes: identification through a proteomic approach|
|Abstract: ||All the spots of the models or showing correlation with one of the mentioned parameters were excised from the gels and identified by LC-MS/MS fragmentation: some of the most important and recurring identification were beta fibrinogen and transaldolase; in particular, 4 spots correspond to beta fibrinogen and 2 spots correspond to transaldolase; all together, these 6 spots contribute to the prediction model in a very remarkable way.
For this reason, we validated by Western blot total beta fibrinogen and transaldolase changes to verify their proper identification and confirm the differences observed by 2-DE with another technique (Western blotting).
Worth of note, the level of some proteins was modified by levodopa and dopamine agonists therapy in T lymphocytes: this is a demonstration that these cells are sensitive to long term dopaminergic stimulation and that they are a valid tool to investigate dopaminergic imbalance at a peripheral level.
Additional experiments were conducted in order to deepen the role of fibrinogen in T cells, and the reason why its volume is reduced in PD patients: this study is currently going on, but preliminary results indicate that it is internalized by T cells from plasma.
In conclusion, in this thesis T lymphocyte proteome changes have been shown to be a valid tool to recognize and classify PD patients. It has been proposed a model using a rationale of similarity between affected cells (dopaminergic neurons) and probed system (T lymphocytes): we expect that our system will reasonably provide information on the effectiveness of future (or under development) drugs designed to interfere with specific cell death mechanisms targeting nigral neurons. Moreover, our system possess most features required for candidate PD biomarkers (specificity, indication of progression, accessibility).
Next step of this research is leading the current finding to the clinical practice. This objective will be reached only through large collaborative networks, that will allow us to select large cohorts of subjects with high heterogeneity in terms of gender, age, ethnicity, clinical phenotype; the use of a different and less time consuming technique in the clinical phase is advisable.|
|Keywords: ||Biomarcatori periferici, Parkinson, linfociti T.|
|Subject MIUR : ||BIO/10 BIOCHIMICA|
|Issue Date: ||2013|
|Doctoral course: ||Neurobiologia|
|Academic cycle: ||25|
|Publisher: ||Università degli Studi dell'Insubria|
|Citation: ||Pippione, A.C.Parkinson's disease biomarkers in peripheral blood T lymphocytes: identification through a proteomic approach (Doctoral Thesis, Università degli Studi dell'Insubria, 2013).|
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